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Updated: Jun 2, 2026

A Novel Procedure for Evaluating the Reinforcing Properties of Tastants in Laboratory Rats: Operant Intraoral Self-administration

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GLP-1 RAs in Substance Use Disorders: Emerging Evidence and Future Directions.

Jason Macanian¹, William H Frishman^1,2

¹From the New York Medical College, Valhalla, NY.

Cardiology in Review

|June 1, 2026

Summary

Glucagon-like peptide-1 receptor agonists (GLP-1RAs) show promise for treating substance use disorders (SUDs) by targeting brain reward circuits. Further research is needed to confirm efficacy and safety for addiction treatment.

Keywords:

GLP-1 receptor agonists alcohol use disorder nicotine addiction opioid use disorder

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Area of Science:

Neuroscience and Pharmacology
Addiction Medicine
Metabolic Disease Research

Background:

Substance use disorders (SUDs) are a major global health burden with limited treatment options.
Current pharmacotherapies for SUDs have moderate efficacy and high relapse rates.
Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are approved for type 2 diabetes and obesity.

Purpose of the Study:

To explore the potential of GLP-1RAs as novel therapeutic agents for SUDs.
To investigate the mechanisms underlying GLP-1RA effects on neural reward circuits.
To review preclinical and early clinical evidence for GLP-1RA efficacy in various substance use models.

Main Methods:

Review of preclinical studies investigating GLP-1RAs in animal models of alcohol, nicotine, and opioid use.
Analysis of early clinical trial data, including studies on semaglutide.
Examination of subgroup analyses and observational data, particularly in individuals with obesity.

Main Results:

Preclinical data show GLP-1RAs reduce drug use, dopamine efflux, and relapse-like behaviors.
Early clinical findings suggest reductions in alcohol and cigarette consumption, though results are inconsistent.
Potential for greater efficacy in individuals with obesity and metabolic disease is suggested.
Animal models for opioid use disorder indicate efficacy comparable to existing treatments.

Conclusions:

GLP-1RAs represent a mechanistically novel therapeutic option for SUDs.
Further large-scale randomized controlled trials are necessary.
Patient stratification and long-term safety assessments are crucial for defining their role in addiction medicine.